In 1990, he was elected to be the first California Insurance Commissioner, serving from 1991 to 1995. Rather than seek re-election, he ran for Governor in the 1994 election, losing in the Democratic primary. He left public office and served as PresidentBill Clinton's Deputy Secretary of the Interior from 1995 to 1998, then worked for the Peace Corps again. He was elected Insurance Commissioner again in 2002 and briefly ran for Governor again in the 2003 recall, before dropping out to support Lieutenant Governor Cruz Bustamante.[2] In 2006, he was elected Lieutenant Governor to succeed the term-limited Bustamante.

While in the California Senate, he served as Majority Leader. His sponsored legislation reformed health care, welfare, and the state tax code. He also protected Lake Tahoe and Mono Lake.[18] He was Chairman of the Joint Committee on Science and Technology, the Senate Health and Welfare Committee, the Senate Revenue and Taxation Committee.[19]

His early years in the office brought him much controversy due to the state seizure of Executive Life Insurance Company, a bankruptcy that was coincidental with the creation of the state Department of Insurance. In addition to this had a number of other accomplishments. He successfully implemented Proposition 103, reforming the auto and homeowner insurance industry. Under his leadership, the department protected homeowners from the Oakland Hills Fire by forcing insurance companies to fully pay for rebuilding. His department earned a reputation as the best consumer protection agency in the nation.[18]

He ran for California Insurance Commissioner for a second time in 2002. He won the Democratic primary with 39% of the vote.[27] In the general election, he defeated Republican Gary Mendoza 46%-42%.[28]

He created a Home Owners Bill of Rights. This helped create laws that reduced workers compensation costs 58% and reduced premiums by over $500 million. He re-established an anti-fraud task force. He also developed a report analyzing California’s health care system with 43 recommended improvements.[18]

Despite living outside of California's 10th congressional district, Garamendi announced his intention to run for the 2009 special election in the 10th district, where Democratic U.S. Congresswoman Ellen Tauscher had vacated her seat. There was some confusion about the location of Garamendi's residence. Garamendi said: "My front yard is in the district, our bedroom is not."[32] Garamendi continued to fuel speculation about the location of his residence when he made similar comments to the NYT in July, stating the same thing. The Sacramento Board of Elections later confirmed that no portion of Garamendi’s property lies within Congressional District 10.

In the September election, no candidate reached the 50% threshold to avoid a run-off election. Garamendi ranked first among Democrats with 26% of the vote, defeating State Senator Mark DeSaulnier (18%) and Assemblymember Joan Buchanan (12%). In the November run-off special election, Garamendi defeated Republican nominee David Harmer 53%-43%.[33][34] After winning the special election on November 3, Garamendi was sworn in as a member of the US House of Representatives on November 5, 2009.[35]

The old 10th Congressional District represented by Garamendi made up just 23% of the new 3rd district. While the old 10th Congressional District traditionally favored Democrats, the new 3rd District is now considered swing district by some.[39] Garamendi defeated Republican Kim Vann 54.2%-45.8%. [40]

John Garmendi actively opposed a GOP-backed construction of a missile defense site on the East Coast, saying it was fiscally irresponsible to be "spending up to $5 billion in the next three years on a missile defense system that doesn't work."[46]

Garamendi is also part of a bipartisan group that wants to challenge "a new law that allows the indefinite detention without trial of suspected terrorists."[47] He also voted against extending the Patriot Act.[48]

Garamendi is married to Patricia W. "Patti" Garamendi, who has worked as Agriculture Specialist for the California Exposition and State Fair and as Deputy Secretary of California's Business, Transportation and Housing Agency. In 1993, she was appointed by President Clinton to serve as Associate Director of the Peace Corps and in 1998 as Deputy Administrator in the Department of Agriculture, Foreign Agricultural Service. They live in Walnut Grove and have six children and nine grandchildren.[53]